Our Modern Scepticism of Plant & Fungi Based Medicines

Growing up as a child of the 90s, it would have been easy to believe the only medicines are the ones found in plastic packaging within drug stores.

This is a stark contrast to the way our human ancestors have lived for thousands of years. In 2018 we found a human jawbone in Israel that was dated to 177,000 years old – the oldest human remains outside of Africa. And if we look at humans within Africa, they go back at least 300,000 years.

So for at least 300,000 years we had nothing in the way of modern pharmaceuticals, and yet survived illness and poor health to propagate our way into the future. Therefore our ancestors, out of necessity (and a lot of trial and error), found medicines growing within nature.

Meet Ötzi, Europe’s oldest known human mummy, found frozen in the Austrian alps. He lived approximately 5,200 year ago. He was found with a number of possessions, including birch bark baskets and two species of polypore mushrooms with leather strings through them! One of these, the birch fungus (Fomitopsis betulina), is known to have anti-parasitic properties, and was probably used for medicinal purposes. The other was a type of tinder fungus (Fomes fomentarius), included with part of what appeared to be a complex firelighting kit, including flint and pyrite for creating sparks.

The modern resistance to ‘natural’ medicine is peculiar, in part because many of the drugs we now take for granted were derived from nature. For example, morphine is derived from poppy seed, the first antibiotic; penicillin, came from a mould that displayed anti bacterial properties, and the natural painkiller and blood thinner aspirin originated from willow bark.

We don’t yet have the engineering capability to imagine, then produce an organism like penicillin from scratch (no doubt it’ll come). Instead we spot functionality in nature that we want, isolate it, and then produce it en mass.

In the same way that we were able to take advantage of penicillin, we have the ability to take advantage of mushrooms to benefit our health.

Well, in some cases they do. A polysaccharide from Turkey Tail mushroom that had anti cancer properties was isolated by the Japanese in the 1960s, patented, and has been used to help treat cancer since.

But to do the same in the USA (e.g. sell Turkey Tail mushroom extract for treating cancer), would require FDA approval. This is a very expensive process (upwards of $1bn), and typically only undertaken where a Pharmaceutical company has patented the molecule and has high expectations of big return on their investment.

According to this Bastyr University article, the traditional use of mushrooms means derivatives are probably not patentable, which has dissuaded pharmaceutical companies from funding clinical trials.

Nonetheless, in 2012 a phase 1 clinical trial for FDA approval was done for Turkey Tail (Trametes Versicolor) mushrooms to treat cancer. However, they need to progress into phase 2 and 3 trials successfully before it would be awarded FDA approval. You can read more about the phase 1 clinical trials here.

Lion’s Mane – Stimulates Nerve Growth

Lets begin then with Lion’s Mane mushroom, also known by the latin Hericium erinaceus. This beautiful mushroom is common during late summer and fall on hardwood trees, particularly American beech. Although when you’re buying it for medicinal purposes, its likely grown indoors, using grain or rice as fuel source. Which is the easiest and cheapest way cultivate it in bulk.

Hericium Erinaceus (above) growing in the wild. The shaggy long needles fall much like the hair on a Lion’s Mane, hence the nickname.

Core Benefit & Potential Uses

Lion’s Mane is able to stimulate the release of nerve growth factor (NGF). NGF has the ability to:

Prevent neuronal death

Promote neurone outgrowth (where an axon or dendrite projects from the cell body of a neuron)

The problem with simply supplementing NGF on its own, is that it can’t cross the blood-brain barrier. However, the hericenones and erinacines compounds in Lion’s Mane are low-molecular weight and easily cross the blood–brain barrier (source), thus benefiting the brain by promoting nerve growth factor once inside.

Neuron components illustrated, including the dendrites and axons mentioned above.

The neat thing is that not only has the NGF functionality of Lion’s Mane been shown in vitro, it has also been demonstrated indirectly in humans. A Japanese randomised controlled trial studied 30 different 50-80 year olds with mild cognitive impairment. By week 8 of supplementation they showed improvements compared to the placebo group (Mori, 2008).

Below is a table of many of the most relevant studies done on Lion’s Mane. There’s a fair amount of “controversy” in the mushroom community regarding the use of mycelium vs the fruiting body. So to aid that discussion I’ve checked the full text to see which version the studies used.

Whilst Lion’s Mane could work as part of a broad mushroom tonic quite effectively (Paul Stamet’s Host Defence include it in a number of their mushroom products). Its strength lies mainly as an enhancer of cognitive function in those at risk of decline. Examples include:

Neurodegenerative diseases such as Alzheimer’s

Brain injuries – either via physical impact or due to stroke

Cognitive decline due to aging

Dosage & Supplement Form

Dosage
For doses related to increased cognitive function, it would make sense to refer to the Japanese paper that showed cognitive improvement in 30 different 50-80 year olds. They consumed 250mg 3x per day, s0 750mg total.

Dosage – upto 750mg/daily

One thing to note is that the Japanese study used the fruiting body of the mushroom, rather than mycelium (which is found in many supplements). Which leads us neatly on to the next discussion…

Do we want Mycelium or the Fruiting Body?

The answer to whether or not we need the fruiting body of Lion’s Mane is still up for debate. It’s relevant because most supplement forms of Lion’s Mane use only the mycelium. Here’s what we do know:

Almost all of the major and noteworthy clinical trials on the mushroom use the fruiting body rather than mycelium

Two compounds in Lion’s Mane known to stimulate Nerve Growth Factor (NGF) are hericenones and erinacines. Hericenones are found in the fruiting body, and erinacines are found in the mycelium (Bing-Ji Ma, 2010). Erinacines are a much more potent stimulator (Kawagishi, 1994) than Hericenones (Kawagishi, 1991). Essentially if you compare the two studies done by Kawagishi and his team, it shows that, in vitro, erinacines were in the range of 10x more potent. However this was being demonstrated on mouse astroglial cells, so in humans the performance is likely to differ.

What this suggests is that the optimal intake method is still not established. There’s an opportunity to re-do some of the clinical trials using fruiting body only, mycelium only and fruiting body + mycelium in order to establish best efficacy. Its quite possible that fruiting body + mycelium (combined) outperforms everything, but we don’t have the data yet to say.

That being said, based on what we know, if your only access is to Lion’s Mane is in mycelium form, this does contain erinacines – which is shown to be a potent activator of nerve growth factor (in vitro).

What you are likely to lose out on when using the Mycelium are Beta glucans (a polysaccharide type). These generally appear in much greater concentration within the fruiting body, and play a useful role in immune system modulation.

The reason for addressing this discussion in a nuanced manner, is that I’ve heard rhetoric that implies mycelium is useless, and the fruiting body is the only useful aspect – and this is an oversimplification.

Something particularly interesting about Lion’s Mane is the amount to which it has been studied and used in Asia. In traditional Chinese and Japanese medicinal practices, it was taken as a tea. Scientists in those countries noticed the healing properties and began extensive clinical research on Lion’s Mane extracts. Two main polysaccharide extracts were isolated; PSK and PSP. After extensive clinical trials, PSK was approved for use in Japan in 1977, and by 1987 sales were worth $357 million (Cui, J – 2003, see full paper). PSP was a Chinese product, and came to market about 10 years after PSK.

I would suggest Yajing Chang’s review paper as a good starting place for researching the mechanisms of action behind Turkey Tail’s polysaccharides. The illustration below is from the paper, and shows PSP’s mechanism of action. PSP being a polysaccharide that’s hot water extracted from turkey tail.

Cancer & Turkey Tail

I think it’s really important to tread carefully around any discussion of cancer treatments. Firstly, I am not a doctor, and therefore any discussion in this post around cancer treatment should not be taken as medical advice. In a very best case scenario, after consultation with your oncologist (doctor who specialises in cancer treatment), turkey tail mushroom would be taken as an addition to what’s called “the standard of care”. Which is typically some form of chemotherapy, radiotherapy and/or surgery. However, its possible that your oncologist does not want turkey tail taken in addition.

Additionally, it’s important to note the inherent complexity around cancer. Cancer is the mutation of DNA cells that results in a harmful, continuously growing cell mass. Mutations happen all the time in the body, but are almost always sniffed out by the bodies natural processes – including the work of tumor suppressing genes. There are lots of different potential mutations, and thus this means most cancers are different. Even lets say, if two people have a cancer in the same location, it will have genetic differences. So as you can imagine, its like trying to hit a moving target. So what works for one cancer, may not for another.

The way to look at turkey tail in relationship to cancer is something like this. The bodies immune system has the capability to tackle some cancers. Turkey tail has the ability to increase our bodies immune function (as best we can tell). This is desirable, and potentially helpful, but not enough on its own.

Paul Stamet’s Turkey Tail Cancer Story

A prominent figure in the fungi world, Paul Stamets has a story on how his mother used turkey tail in addition to the standard care, to help beat a cancerous tumor in her breast. The video below details the story:

Dosage & Supplement Form

To be updated.

General Medicinal Mushroom Notes

Terminology & Background Info

Paul Stamets

Difference between Mycelium & Fruiting Body

Generally when we think of mushrooms, we think of the visible part we see above the surface, in a typical mushroom looking shape. However, there is more going on than meets the eye. The unseen organism that creates these beautiful mushrooms looks like a web of white threads (known as hyphae). A comparison can be drawn to a plant and its fruit. The life sustaining organism is the plant (or in our case mycelium), and the reproductive aspect is the fruit (for us the mushroom). Hence the reason for calling mushrooms; ‘fruiting body’. Mushrooms produce spores that get released into the air, land at a new site, and germinate. When two compatible mycelia join, they have the potential to form more fruiting bodies.

Mycelium Controversy

Many products contain only Mycelium, no Fruiting Body, is this okay?

With medicinal mushrooms, there are typically 3 different ways of having them:

Mycelium powder

Fruiting body powder

Hot water and alcohol based extracts of either mycelium or fruiting body

Perhaps the most common source is the mycelium, which is cheaper and quicker to produce in bulk than the fruiting body. There’s a lot of scepticism online as to whether or not this is okay, lets dig into it.

Mycelium Powder

The most common method of producing high yields of mushrooms is to grow them on straw or rice substrates. When you intend to harvest the mycelium rather than the fruiting body, it makes sense to use a substrate such as rice, which is edible. This is because the mycelium becomes so intertwined in the substrate, that it’s not possible to separate the colonised sections. Thus the supplement will end up with a certain amount of substrate in it.

Mycelium Powder Controversy

Mushrooms and mycelium contain a number of different compounds that have varying effects. For example, there are polysaccharides (e.g. beta-glucans and glycoproteins) and antioxidants (e.g. terpenes, triterpenoids, inositols, ergosterols, sterols and myco-flavonoids). These compounds are not necessarily evenly distributed between the mycelium and the fruiting body, and thus when taking medicinal mushrooms its important you are consuming the part of the fungi that contains the beneficial properties you are seeking.

That being said… we shouldn’t blanket demonise mycelium powders as non-optimal (unfortunately there does seem to be some of this sentiment online). Ideally you know what particular benefits you’re looking for, and search the literature to understand if this is solely found in the fruiting body, or can also be found in the mycelium.

Lets take Lion’s Mane for instance, the literature suggests that the Nerve Growth Factor (NGF) properties many people desire from the organism are conveyed through its hericenones and erinacines content. Lets then say that a Lion’s Mane mycelium extract was being criticised for its lack of beta glucans, well, this would miss the point, as it’s not the beta glucans that give it its key property.

Additionally, there is a more added complexity to be aware of, for example:

Mushrooms strains age, like other living organisms, and so if your mushroom product comes from an old strain, its possible it does contain all the beneficial compounds found in identical strains growing in the wild (read more about this phenomenon).

That being said, it’s definitely important to stay alert and sceptical when analysing your choice of products.

Closing Words

This post is inspired by the work of Paul Stamets who brought the medicinal properties of mushrooms to my attention. Specifically it was a show he did with Joe Rogan (YouTube link) – worth a watch if you haven’t seen it.